Epidermal growth factor receptor (EGFR) (HER I) is a member of the tyrosine kinase family (Type 1) of cell surface receptors, for which several peptide ligands have been reported, including epidermal growth factor (EGF), transforming growth factor-α (TGF-α), vaccinia growth factor, amphiregulin, and cripto. Ligand binding to EGFR stimulates mitogenesis, and overexpression of EGFR has been associated with increased tumor growth, metastasis, and/or adverse outcome in numerous epithelial cancers, including squamous cell carcinomas of the head and neck (SCCHN) (1,2). Many human tumor cells express high levels of EGFR, raising the possibility that receptor-directed therapies may be useful as anticancer strategies. Such treatment has included monoclonal antibodies directed against EGFR (3-6) or fusion proteins/immunotoxins against TGF-α/EGFR using toxins elaborated by Pseudomonas or Diphtheria species (7,8).
EGFR antisense-expression plasmids have been shown to block translation of EGFR messenger RNA (mRNA) and suppress the transforming phenotype of pharyngeal carcinoma (KB) cells in vitro (9). Targeting EGFR via several different approaches, including suppression of EGFR mRNA using anti-sense oligonucleotides, and blocking the function of the mature protein at two sites, the ligand-binding domain and the kinase domain, we previously demonstrated inhibition of proliferation of SCCHN but not normal mucosal squamous epithelial cells (10). Nevertheless, due to the inherent unpredicatbility in antisense technology and the inability to extend in vitro findings to in vivo in antisense therapies, an effective in vivo antisense therapy is desired.